Human chromosome banding techniques have revolutionized the study of metaphase chromosomes by light microscopy. Generation of characteristic patterns of bands (i.e., differential staining along a chromosome) has allowed routine identification of each of the human chromosomes as well as precise identification of deleted or translocated fragments of chromosomes. Many deletions and translocations have been directly correlated with developmental abnormalities. Numerous chromosome aberrations are clinically recognized, bringing the latest technology into the clinical world of diagnosis and treatment. So far, clinical studies have relied on examination of banded chromosomes by light microscopy. The possibility that electron microscopic methods might powerfully increase the understanding of genetic diseases by revealing more detailed banding patterns in manifest. In principle much more precise localization of break points and much more specific identification of deleted, translocated, and trisomic material could be achieved by employing the higher resolving power of the electron microscope. Electron microscopy of banded chromosomes has been hampered by the unavailability of a suitable banding method. In general heavy atom stains must be used instead of organic dyes to generate sufficient contrast in the electron micrographs. We propose the development of a method for electron microscopic banding of human chromosomes and its application to normal and abnormal human chromosomes. We also propose to use it in the clinical analysis of defective chromosomes. The importance of this work lies in its potential to dramatically increase the precision with which human chromosome aberrations can be studied. As a powerful new diagnostic tool, it may allow the correlation of abnormal development with very slight and otherwise undectable chromosome defects. The technique might bring closer the day when normal human development will be understood and abnormal development controlled.